Spanish research results create vaccine that induces viral control without ART in a significant percentage of subjects

checking vaccine 25A vaccine known as the "HIV Vaccine" vaccine, for the first time, produced significant response in prolonged viral control in a large minority of recipients, once they were withdrawn from antiretroviral therapy (ART). So far one participant has been out of ART for seven months without having to resume. Introducing Conference on Retroviruses and Opportunistic Infections (CROI 2017), Beatriz Mothe said that, viral control in subjects of this vaccine, occurred more frequently than spontaneous control of HIV, observed in previous studies of discontinuation of treatment.

Although a number of vaccine studies in monkeys have produced viral suppression for the long term, this is the first human study that produced such an effect.

HIV Conserving Vaccines and the BCN01 Study

The study of the BCN02 vaccine is still ongoing and is following a single study dose, BCN01, which researcher Beatriz Mothe reported last year (see reference).

The first study recruited 15 people who started treatment shortly after HIV infection and gave them a single dose of an HIV vaccine vaccine (or 'HIVconsv').

For a fuller explanation of what HIV Conserves Vaccines are and how they work See this report (in English and on another tab). In brief explanation, they contained selected antigens (immune-stimulating sequences of proteins or genes) from HIV that are highly conserved, hence the name. "Highly conserved" means that they are the parts of HIV that the virus can change less often, and that vary little in the many variants of HIV.

The vaccine thus consists of protein sections from different "aggregate" HIV strains that generate a strong immune response to HIV, which the virus finds difficult to "escape." HIV can not be "to afford to generate mutations that circumvent the body's immune responses because it would weaken it ".

What this means is that the vaccine "pushes" the cellular mechanism of anti-HIV cells from "T CDXNX" cells into a response to become more potent with less waste because the body does not generate responses from which the virus can easily escape. In the BCN8 study of the researchers it was established that this was exactly what had happened.

linfocito-depositphotos_49757357_original_vectBlood cell Lymphocyte

Study BCN02

For the second study the researchers worked with the same cast with the 15 participants, giving them two more doses of the vaccine "HIV Conserv"In 0 and 9 weeks. In addition, in the weeks 3, 4 and 5, three infusions of the "Latency Inverter" romidepsin, which is an immune system stimulant drug, have been applied in the so-called 'kick and kill' cure studies of HIV infection in experiments of cure.

The idea of ​​using an HIV vaccine combined with romidepsin is to use romidepsin to stimulate viral production bursts (the awakening of viral reservoirs) while the viral participant is still under antiretroviral therapy (ART). The immune response stimulated by the vaccine "sees" these bouts of viral replication, reinforcing itself, and thus to a fine-tuning of this response.

HIV DNA in cells was measured at week 0, weeks 3 to 5 while romidepsin was being given, and at week 9. The proportion of CD8 cells that were effectively destructive to HIV was measured at weeks 0, 1, 3, 9, 10 and 13. The ART was stopped at the 17th week in a paused monitored pause of antiretrovirals. ART was resumed in subjects who had a viral rebound.

Results

There were 14 men and 1 woman in the study. The mean age was 40 years and all had started ART early - an average of three months and a maximum of 5 months from the estimated date of HIV infection. All had been on ART for more than three and four years. All of them were under schemes containing integrase inhibitor and their average count of CD4 was 728 cells / mm3 (416 minimum).

The vaccine produced led to symptoms such as those of the flu and the most common side effects were headache, fatigue and muscle aches.

The three infusions of romidepsin were accompanied by short bursts of viral production, despite ART, in the order of 50 for 400 copies / ml, with some viral blots of 1000 copies / ml, in all but one participant. These were accompanied by similar T cell production waves: CD4 counts rose by about 200 cells / mm3 during each infusion, but were back to the previously observed threshold after three days. Translator's note: For curiosity I went "to find out more about this" romidesepin "and found something, in wikipedia, in English and follows below:

The romidepsina, also known as Istodax is an anticancer agent used in cutaneous T-cell lymphoma (CTCL) and other peripheral T cell lymphomas (PTCLs). Romidepsin is a natural product obtained from the bacterium Chromobacterium violaceum, and works by blocking enzymes known as histone deacetylases, thereby inducing apoptosis. [1] It is sometimes referred to as depsipeptide after the class of molecules to which it belongs. Romidepsin is marked and owned by Gloucester Pharmaceuticals, now a part of Celgene. [2]

Adverse effects The use of romidepsin is uniformly associated with adverse effects. [13] In clinical trials, the most common were nausea and vomiting, fatigue, infection, loss of appetite and blood disorders (including anemia, thrombocytopenia, and leukopenia). It has also been associated with infections and metabolic disorders (such as abnormal levels of electrolytes), cutaneous reactions, altered palate perception and changes in cardiac electrical conduction. [13]

This is an overview of something that I considered important to put here. Who want to know more just click Romidesepin - Opens in another tab, is in English but the Tgoogle radutor help excellent way

White Keyboard with Vaccination Button.

Despite these peaks of viral production, the amount of viral DNA in reservoir cells did not change: a hope provided by the original 'kick and kill' concept was that outbreaks of viral production would be a "storm" of infected cells, but this does not seem to happen.

The anti-HIV responses of CD8 cells increased during the study, both after the first dose of vaccine as well as after the introduction of romidepsin. But equally important, the type of immune response was characterized by a broad response to all HIV proteins to a situation in which three quarters of the immune response was quite aggressive to the highly conserved areas targeted by the vaccine.

Shutting down the viral control by ART

So far thirteen of the fifteen study participants have discontinued their antiretroviral therapies. For 8 of 13, viral load rapidly jumped to pre-ART levels (average of about 100.000 copies / ml) within four weeks and they started again

Antiretroviral Therapy
It's not always like that. There are schemes with three tablets a day, once a day. As an example the combination of lamivudine in one tablet, associated with atazanavir, a capsule and Norvir, a tablet relativaemete small once daily.

.

However, for the other five participants, the viral load only jumped intermittently to low levels (below 2000 copies / ml). So far, these five participants have remained out of their ART after 6, 12, 19, 20 and 28 weeks, respectively. None have maintained completely undetectable levels of viral load during this time; instead what has been seen is a pattern of "blipes", especially the 200 copies / ml or so, but there was a case of 2000 copies / ml, before becoming undetectable again. One participant (at 19th week without ART) had a slightly different pattern; initially it kept suppressed its viral load which suddenly jumped to 2000 copies / ml in the seventh week and meanwhile, from the twelfth week, began to decline and is now below 200 copies / ml.

These five participants represent 38% of the group that is considerably higher than 2% of people who normally control their viral load after stopping ART.

What made the difference between being a bounder and a "controller"?

The proviral DNA in cells mattered: the controllers were all within the bottom half of the viral load measurement checks. There was no correlation with the intensity of the immune response, but there was a correlation with its specificity: all controls had a higher proportion of their immune responses tuned to the highly conserved regions of HIV.

Conclusions

It seems that if the vaccine has contributed to reinforce a phenomenon sometimes seen in people who very soon start treatment after infection. Such people naturally develop smaller reservoirs of RNA and therefore, preserve some degree of immune control of HIV more effective because there is a lack of proliferation of viral strains that occurs in people not treated chronically. This proliferation overwhelms the ability of your immune system to adapt to it. Not only does the vaccine reinforce this helpful response, it also redirects the immune response more efficiently.

"This study is interesting because it is the first to demonstrate post-treatment control - which is, by definition, the following:

The virus is present but there is no viral rebound after stopping antiretroviral therapy, "said Sharon Lewin, Director of the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Australia. "But we also have to be cautious - there was no control group and we do not know which part of the intervention was important - the start of the vaccine? The second vaccine? Romidepsin? All the above?

"At the same time so far in all other studies involving discontinuation of treatment, and post-treatment control was rare and mostly happens occasionally. This is a promising and significant step forward. No doubt we need a follow-up study that is larger, as well as having a control group that does not receive any intervention and a less complicated vaccination schedule. We would like to understand why some people control the infection at non-dangerous levels as well - and for truth's sake, at this point we do not know the answer to that. "

Translated by Cláudio Souza from the original in English at the address below Spanish control viral vaccine induces off ART in Nearly 40% of recipients Originally published by Gus Cairns on 17 February of 2017 for AIDSMAP.com

Reviewed by Mara Macedo

References

Mothe B et al. Viral control induced by vaccines HIVconsv & Romidepsin in early treated Individuals. Conference on Retroviruses and Opportunistic Infections (CROI 2017), Seattle, abstract 119LB, 2017.

View the abstract on the conference website.

View the webcast of this presentation on the conference website.

See also Mothe B et al. Shaping CTL Immunodominance With Conserved HIV Vaccines After Early Treatment (BCN01). CROI 2016, Boston, abstract in 320, 2016.

View the abstract on the conference website

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